Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability - PubMed (original) (raw)

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Matrix Metalloproteinases as Biomarkers of Atherosclerotic Plaque Instability

Wioletta Olejarz et al. Int J Mol Sci. 2020.

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling and degradation of extracellular matrix (ECM) proteins. MMPs may modulate various cellular and signaling pathways in atherosclerosis responsible for progression and rupture of atherosclerotic plaques. The effect of MMPs polymorphisms and the expression of MMPs in both the atherosclerotic plaque and plasma was shown. They are independent predictors of atherosclerotic plaque instability in stable coronary heart disease (CHD) patients. Increased levels of MMPs in patients with advanced cardiovascular disease (CAD) and acute coronary syndrome (ACS) was associated with future risk of cardiovascular events. These data confirm that MMPs may be biomarkers in plaque instability as they target in potential drug therapies for atherosclerosis. They provide important prognostic information, independent of traditional risk factors, and may turn out to be useful in improving risk stratification.

Keywords: atherosclerosis; biomarkers; doxycycline; matrix metalloproteinases (MMPs); statins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Structure of matrix metalloproteinases (MMPs). Catalytic domain contains Zn2+ in the active site. Signal sequence and prodomain are removed during the proteolytic activation of pro-MMPs. Cysteine-rich switch is essential for the activation of MMPs. The hinge region serves as a linker between the catalytic domain and C-terminal domain.

Figure 2

Figure 2

MMPs in atherosclerotic plaque. MMP-2 causes lymphocytes infiltration while MMP-2 and MMP-9 causes endothelial cells (EC) migration. MMP-7 activity leads to vascular smooth muscle cells (VSMC) apoptosis, contributing to plaque instability. Activated VSMCs produce high-mobility group box 1 (HMGB1) which affects the expression of MMP-2, MMP-3, and MMP-9 and enhances plaque rupture. MMP-1, MMP-8, MMP-9, MMP-12, MMP-13, and MMP-14 trigger similar effect by extracellular matrix (ECM) degradation within the fibrous cap that causes plaque rupture.

Figure 3

Figure 3

MMPs as biomarkers in cardiovascular diseases.

References

    1. Nagase H., Visse R., Murphy G. Structure and function of matrix metalloproteinases and timps. Cardiovasc. Res. 2006;69:562–573. doi: 10.1016/j.cardiores.2005.12.002. - DOI - PubMed
    1. MacColl E., Khalil R.A. Matrix metalloproteinases as regulators of vein structure and function: Implications in chronic venous disease. J. Pharmacol. Exp. Ther. 2015;355:410–428. doi: 10.1124/jpet.115.227330. - DOI - PMC - PubMed
    1. Marino-Puertas L., Goulas T., Gomis-Ruth F.X. Matrix metalloproteinases outside vertebrates. Biochim. Biophys. Acta Mol. Cell Res. 2017;1864:2026–2035. doi: 10.1016/j.bbamcr.2017.04.003. - DOI - PubMed
    1. Gupta S.P. Matrix metalloproteinase inhibitors: Specificity of binding and structure-activity relationships. Exp. Suppl. 2012;103:v–vi. - PubMed
    1. Chen Q., Jin M., Yang F., Zhu J., Xiao Q., Zhang L. Matrix metalloproteinases: Inflammatory regulators of cell behaviors in vascular formation and remodeling. Mediators Inflamm. 2013;2013:928315. doi: 10.1155/2013/928315. - DOI - PMC - PubMed

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